Stable verapamil hydrochloride sustained-release capsule and preparation method thereof

Abstract

The invention provides a verapamil hydrochloride sustained-release capsule with stable release rate during storage, the sustained-release capsule content comprises a sustained-release coated pellet, and the sustained-release coated pellet comprises (a) a blank pellet core, (b) a drug coating layer wrapping the blank pellet core, and (c) a sustained-release coating layer wrapping the drug coating layer; the drug coating layer comprises verapamil hydrochloride and a release stabilizer, and the in-vitro release degree similarity factor f2 of the sustained-release capsule after being placed for a long time under the conditions of 40 DEG C and RH of 75% and the sustained-release capsule before being placed is greater than 50. The verapamil hydrochloride sustained-release capsule effectively solves the problem that the in-vitro release degree is unstable in the storage process of the verapamil hydrochloride sustained-release capsule, and the clinical medication safety of the preparation within the storage validity period is greatly improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of pharmaceutical preparations, in particular to a verapamil hydrochloride sustained-release capsule and a preparation method thereof. BACKGROUND

[0002] Hypertension is a common cardiovascular and cerebrovascular disease with high mortality and disability rate, which is closely related to individual living habits. Late sleep, overeating, and excessive work pressure are potential factors for hypertension. The current population aging in China leads to an increasing number of hypertensive patients, and thus the prevention and treatment of elderly hypertension is very important. Studies have shown that the key to hypertension treatment is the treatment time, and the administration combined with the characteristics of circadian rhythm can greatly reduce the incidence rate. Another key is the speed and amplitude of blood pressure reduction, and rapid and large amplitude reduction of blood pressure can cause damage to target organs. For essential hypertension, drug treatment is more effective, and antihypertensive drugs can be divided into five categories according to the mechanism of action. Calcium antagonists have a significant effect, high safety, and can be used for long-term treatment, and are the most commonly used antihypertensive drugs.

[0003] Verapamil hydrochloride is a benzylamine selective calcium channel blocker, also known as isoprotend and verapamil, which is a white powder, odorless, easily soluble in methanol, ethanol or chloroform, and soluble in water. As a commonly used antihypertensive calcium antagonist, verapamil hydrochloride can regulate the ion concentration of cardiac L-type calcium channels to reduce heart rate and blood pressure. It not only has the effect of regulating blood pressure, but also can treat angina pectoris and inhibit vascular calcification. The sustained-release preparation of verapamil hydrochloride does not have the common phenomenon of reflex tachycardia, can improve renal circulation, has definite clinical efficacy and few side effects, and has a protective effect on target organs. At present, the verapamil hydrochloride preparations on the market at home and abroad are conventional tablets and sustained-release tablets. These preparations may have problems of changes in drug release during storage, and therefore it is urgent to develop a verapamil hydrochloride preparation with good drug release stability within the shelf life. SUMMARY

[0004] To solve the above technical problems, the present application includes the following aspects: The first aspect of the present application provides a method for improving the release stability of verapamil hydrochloride sustained-release capsules during storage. The content of the sustained-release capsule comprises sustained-release coated pellets, and the sustained-release coated pellets comprise: (a) a blank pellet core, (b) a drug coating layer wrapped outside the blank pellet core, and (c) a sustained-release coating layer wrapped outside the drug coating layer; the method comprises adding a release stabilizer to the drug coating layer containing verapamil hydrochloride, and the similarity factor f2 of the in vitro release of the sustained-release capsule after long-term storage at 40°C and RH 75% is greater than 50 compared with that before storage.

[0005] Preferably, the release stabilizer is selected from one or more of hydroxypropyl methylcellulose, ethyl cellulose. More preferably, the release stabilizer is selected from one or more of hydroxypropyl methylcellulose E5, ethyl cellulose N7. Further preferably, the release stabilizer is ethyl cellulose N7 or a combination of hydroxypropyl methylcellulose E5 and ethyl cellulose N7.

[0006] Preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 10-30%. More preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 12-26%. Further preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 19-26%.

[0007] Preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 10-30%. More preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 12-26%. Further preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 19-26%.

[0008] Preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 10-30%. More preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 12-26%. Further preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 19-26%.

[0009] Preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 10-30%. More preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 12-26%. Further preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 19-26%.

[0010] Preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 10-30%. More preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 12-26%. Further preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 19-26%.

[0011] Preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 10-30%. More preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 12-26%. Further preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 19-26%.

[0012] Preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 10-30%. More preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 12-26%. Further preferably, the release stabilizer is present in the extended release capsule contents in a weight percentage of 19-26%.

[0013] Preferably, the plasticizer is selected from one or more of triethyl citrate, diethyl phthalate, dibutyl sebacate.

[0014] Preferably, the plasticizer is present in the extended release capsule contents in a weight percentage of 0.5-2.5%. More preferably, the plasticizer is present in the extended release capsule contents in a weight percentage of 0.8-2%. Further preferably, the plasticizer is present in the extended release capsule contents in a weight percentage of 1.0-1.6%.

[0015] Preferably, the anti-tacking agent is selected from one or more of magnesium stearate, glyceryl monostearate, talc. More preferably, the anti-tacking agent is selected from one or more of talc, glyceryl monostearate. Further preferably, the anti-tacking agent is talc or glyceryl monostearate.

[0016] Preferably, the anti-tacking agent is present in the extended release capsule contents in a weight percentage of 0.1-2%. More preferably, the anti-tacking agent is present in the extended release capsule contents in a weight percentage of 0.2-1.5%. Further preferably, the anti-tacking agent is present in the extended release capsule contents in a weight percentage of 0.3-1%.

[0017] Preferably, the contents of the extended release capsule further comprise a lubricant.

[0018] Preferably, the lubricant is selected from one or more of talc, colloidal silicon dioxide, and magnesium stearate. More preferably, the lubricant is selected from one or more of talc and magnesium stearate. Further preferably, the lubricant is magnesium stearate or talc.

[0019] Preferably, the lubricant is present in the extended release capsule contents in a weight percentage of 0.1-2%. More preferably, the lubricant is present in the extended release capsule contents in a weight percentage of 0.5-1.5%. Further preferably, the lubricant is present in the extended release capsule contents in a weight percentage of 0.8-1.2%.

[0020] Preferably, the extended release capsule of verapamil hydrochloride comprises a 96.8 mg sucrose pellet, 300 mg verapamil hydrochloride, 62.9 mg hydroxypropyl methylcellulose E5 (release stabilizer), 42.1 mg ethyl cellulose N7 (extended release material), 6.3 mg dibutyl sebacate (plasticizer), 2.1 mg glyceryl monostearate (anti-tacking agent), and 5.4 mg talc (lubricant).

[0021] Preferably, the sustained release verapamil hydrochloride capsule comprises 96.8 mg sucrose pellet, 300 mg verapamil hydrochloride, 111.3 mg hydroxypropyl methylcellulose E5 (release stabilizer), 42.1 mg ethyl cellulose N7 (sustained release material), 6.3 mg dibutyl sebacate (plasticizer), 2.1 mg glyceryl monostearate (anti-sticking agent), and 5.4 mg talc (lubricant).

[0022] Preferably, the sustained release verapamil hydrochloride capsule comprises 96.8 mg sucrose pellet, 300 mg verapamil hydrochloride, 159.3 mg hydroxypropyl methylcellulose E5 (release stabilizer), 42.1 mg ethyl cellulose N7 (sustained release material), 6.3 mg dibutyl sebacate (plasticizer), 2.1 mg glyceryl monostearate (anti-sticking agent), and 5.4 mg magnesium stearate (lubricant).

[0023] Preferably, the sustained release verapamil hydrochloride capsule comprises 96.8 mg sucrose pellet, 300 mg verapamil hydrochloride, 111.3 mg hydroxypropyl methylcellulose E5 (release stabilizer), 63.1 mg Eudragit RS (sustained release material), 9.5 mg diethyl phthalate (plasticizer), 6.3 mg talc (anti-sticking agent), and 6.3 mg magnesium stearate (lubricant).

[0024] Preferably, the sustained release verapamil hydrochloride capsule comprises 96.8 mg sucrose pellet, 300 mg verapamil hydrochloride, 87.1 mg ethyl cellulose N7 (release stabilizer), 42.1 mg ethyl cellulose N7 (sustained release material), 6.3 mg dibutyl sebacate (plasticizer), 2.1 mg glyceryl monostearate (anti-sticking agent), and 5.4 mg talc (lubricant).

[0025] Preferably, the sustained release verapamil hydrochloride capsule comprises 96.8 mg sucrose pellet, 300 mg verapamil hydrochloride, 111.3 mg ethyl cellulose N7 (release stabilizer), 42.1 mg ethyl cellulose N7 (sustained release material), 6.3 mg dibutyl sebacate (plasticizer), 2.1 mg glyceryl monostearate (anti-sticking agent), and 5.4 mg talc (lubricant).

[0026] Preferably, the sustained release verapamil hydrochloride capsule comprises 96.8 mg sucrose pellet, 300 mg verapamil hydrochloride, 159.3 mg ethyl cellulose N7 (release stabilizer), 42.1 mg ethyl cellulose N7 (sustained release material), 6.3 mg dibutyl sebacate (plasticizer), 2.1 mg glyceryl monostearate (anti-sticking agent), and 5.4 mg talc (lubricant).

[0027] Preferably, the verapamil hydrochloride sustained-release capsule comprises 96.8 mg sucrose pellet core, 300 mg verapamil hydrochloride, 16.7 mg hydroxypropyl methylcellulose E5 (release stabilizer), 94.6 mg ethyl cellulose N7 (release stabilizer), 63.1 mg Eudragit RS (sustained-release material), 9.5 mg triethyl citrate (plasticizer), 6.3 mg talc (anti-adhesion agent) and 6.3 mg magnesium stearate (lubricant).

[0028] Preferably, the long-term storage time is more than 1 month. More preferably, the long-term storage time is more than 3 months. Further preferably, the long-term storage time is more than 6 months.

[0029] Preferably, the similarity factor f2 of the in-vitro release rate of the sustained-release capsule after long-term storage at 40°C and RH 75% and the sustained-release capsule before storage is greater than 55, or greater than 60, or greater than 65, or greater than 70, or greater than 75, or greater than 80, or greater than 85, or greater than 90, or greater than 95.

[0030] The second aspect of the present application provides a verapamil hydrochloride sustained-release capsule with release stability during storage, wherein the content of the sustained-release capsule comprises sustained-release coated pellets, and the sustained-release coated pellets comprise: (a) a blank pellet core, (b) a drug coating layer wrapped outside the blank pellet core, and (c) a sustained-release coating layer wrapped outside the drug coating layer; the drug coating layer comprises verapamil hydrochloride and a release stabilizer, and the similarity factor f2 of the in-vitro release rate of the sustained-release capsule after long-term storage at 40°C and RH 75% and the sustained-release capsule before storage is greater than 50.

[0031] Preferably, the release stabilizer is selected from one or more of hydroxypropyl methylcellulose and ethyl cellulose. More preferably, the release stabilizer is selected from one or more of hydroxypropyl methylcellulose E5 and ethyl cellulose N7. Further preferably, the release stabilizer is ethyl cellulose N7 or a combination of hydroxypropyl methylcellulose E5 and ethyl cellulose N7.

[0032] Preferably, the weight percentage of the release stabilizer in the content of the sustained-release capsule is 10-30%. More preferably, the weight percentage of the release stabilizer in the content of the sustained-release capsule is 12-26%. Further preferably, the weight percentage of the release stabilizer in the content of the sustained-release capsule is 19-26%.

[0033] The third aspect of the present application provides a preparation method of the above verapamil hydrochloride sustained-release capsule, which comprises the following steps: (1) dissolving the prescription amount of verapamil hydrochloride and release stabilizer material in a mixed solvent to prepare a drug-containing coating solution; (2) slowly spray the drug-containing coating solution prepared in step (1) onto the prescribed amount of the blank pellet cores in a fluidized bed coater, so that the blank pellet cores are coated with the drug-containing coating layer, and then dried to obtain the drug-containing pellets; (3) dissolve the prescribed amount of the sustained-release material, the plasticizer and the anti-adhesion agent in a solvent to prepare a sustained-release coating solution; (4) slowly spray the sustained-release coating solution prepared in step (3) onto the drug-containing pellets prepared in step (2) in a fluidized bed coater, so that the drug-containing pellets are coated with the sustained-release coating layer, and then dried to obtain the sustained-release coated pellets; (5) mix the sustained-release coated pellets prepared in step (4) with the lubricant, and then fill into a capsule to obtain the final product.

[0034] Preferably, the mixed solvent in step (1) is a mixture of ethanol and water. More preferably, the mixed solvent in step (1) is a mixture of ethanol and water with a volume ratio of 8:2 to 3:7.

[0035] Preferably, the weight ratio of verapamil hydrochloride to the mixed solvent in step (1) is (10-30):100. More preferably, the weight ratio of verapamil hydrochloride to the mixed solvent in step (1) is 20:100.

[0036] Preferably, the solvent in step (3) is ethanol.

[0037] Preferably, the weight ratio of the sustained-release material, the plasticizer and the anti-adhesion agent to the solvent in step (3) is (5-15):100. More preferably, the weight ratio of the sustained-release material, the plasticizer and the optional anti-adhesion agent to the solvent in step (3) is 12:100.

[0038] Preferably, the fluidized bed coating parameters in step (2) are set as follows: the inlet air temperature is 40-50°C, the material temperature is 35-45°C, the atomization pressure is 1.0-2.0 bar, the air flow is 80-150 cfm, the inner barrel height is 2-6 cm, the humidity is not more than 30%, and the flow rate is 5-30 g / min. More preferably, the fluidized bed coating parameters in step (2) are set as follows: the inlet air temperature is 45°C, the material temperature is 40°C, the atomization pressure is 1.5 bar, the air flow is 110 cfm, the inner barrel height is 3-5 cm, the humidity is not more than 20%, and the flow rate is 10-20 g / min.

[0039] Preferably, the fluidized bed coating parameters in step (4) are set as follows: inlet air temperature is 30-40℃, material temperature is 30-40℃, atomization pressure is 1.0-2.0 bar, air volume is 80-150 cfm, inner barrel height is 2-5 cm, humidity is 20-40%, and flow rate is 5-20 g / min. More preferably, the fluidized bed coating parameters in step (4) are set as follows: inlet air temperature is 38℃, material temperature is 32℃, atomization pressure is 1.5 bar, air volume is 110 cfm, inner barrel height is 3 cm, humidity is 25-35%, and flow rate is 10-15 g / min.

[0040] The fourth aspect of the present application provides use of the above verapamil hydrochloride sustained-release capsule in preparation of a medicament for treating primary hypertension, angina pectoris or arrhythmia.

[0041] The present application has the following technical effects: The content of the verapamil hydrochloride sustained-release capsule of the present application is a sustained-release coated pellet with a drug-containing coating layer containing verapamil hydrochloride and a specific release stabilizer material (e.g., hydroxypropyl methylcellulose E5, ethyl cellulose N7) and a sustained-release coating layer successively coated on a blank pellet core. The sustained-release capsule of the present application has a similarity factor f2 of 50 or more to the release degree of the initial preparation after being placed at 40℃, RH 75% for 6 months, effectively solving the problem of unstable in-vitro release degree of the verapamil hydrochloride sustained-release capsule during storage, and greatly improving the clinical medication safety of the preparation within the storage validity period. DETAILED DESCRIPTION

[0042] Test Example 1, in-vitro release test of the verapamil hydrochloride sustained-release capsule of the present application 1. Test method 1.1. Preparation of sustained-release capsules (1) Prescription The prescriptions of Examples 1-8 of the present application are shown in the following table (the unit dose drug content is 300 mg, and each auxiliary material is in mg).

[0043] The prescriptions of Comparative Examples 1-5 of the present application are shown in the following table (the unit dose drug content is 300 mg, and each auxiliary material is in mg).

[0044] (2) Preparation process The preparation methods of Examples 1-8 and Comparative Examples 1-5 are as follows: 1) Dissolve the prescribed amount of verapamil hydrochloride and release stabilizer material in a mixed solvent (Examples 1-4 and Comparative Examples 1, 3-5 were dissolved in a mixed solvent of ethanol and water at a weight ratio of 3:7, and Examples 5-8 and Comparative Example 2 were dissolved in a mixed solvent of ethanol and water at a weight ratio of 8:2), to prepare a drug-containing coating solution, wherein the weight ratio of verapamil hydrochloride to the mixed solvent is 20:100; 2) Place the prescribed amount of the pellet core in a fluidized bed coater, and slowly spray the drug-containing coating solution prepared in step 1) into the fluidized bed, to coat the pellet core with a drug-containing coating layer, thereby preparing a drug-containing pellet; the fluidized bed coating parameters of this step are as follows: inlet air temperature is 45°C, material temperature is 40°C, atomization pressure is 1.5 bar, air volume is 110 cfm, inner barrel height is 3-5 cm, humidity is not more than 20%, and flow rate is 10-20 g / min; 3) Dissolve the prescribed amount of release material, plasticizer, and anti-adhesion agent in ethanol, to prepare a release coating solution, wherein the weight ratio of the combination of release material, plasticizer, and anti-adhesion agent to ethanol is 12:100; 4) Slowly spray the release coating solution prepared in step 3) into the fluidized bed, to coat the drug-containing pellet obtained in step 2) with a release coating layer, thereby preparing a release-coated pellet; the fluidized bed coating parameters of this step are as follows: inlet air temperature is 38°C, material temperature is 32°C, atomization pressure is 1.5 bar, air volume is 110 cfm, inner barrel height is 3 cm, humidity is 30%, and flow rate is 5-15 g / min; 5) Dry the release-coated pellet prepared in step 4) in a fluidized bed; the fluidized bed coating parameters of this step are as follows: inlet air temperature is 55°C, material temperature is 50°C, air volume is 110 cfm, inner barrel height is 3 cm, humidity is less than 10%, and drying time is 2 hours; 6) Mix the release-coated pellet prepared in step 5) with a lubricant, and fill into a capsule, thereby obtaining the product.

[0045] The amount of verapamil hydrochloride used in each batch of the above method is 800 g, and the amounts of the remaining excipients are calculated based on the unit dose of the aforementioned prescription.

[0046] 1.2, Release Capsule Dissolution Test The verapamil hydrochloride sustained-release capsules of Examples 1-8 and Comparative Examples 1-5 were packaged in high-density polyethylene bottles, with a packaging specification of 30 capsules per bottle, and placed in a 40℃, RH 75% environment. Samples were taken at 0, 1, 3 and 6 months, respectively, to investigate the drug release of the sustained-release capsules at different sampling times. The paddle method was used to determine the release of each formulation, with a dissolution medium volume of 0.1N HCl, 900 mL. Samples were taken at 1 h, 2 h, 4 h, 6 h, 8 h, 12 h to determine the release of verapamil hydrochloride (%), with a detection wavelength of UV 278 nm. The dissolution similarity factor f2 of each example and comparative example was calculated compared with the initial sample (0 month sample).

[0047] The release results of the verapamil hydrochloride sustained-release capsules of Examples 1-8 of the present application at different storage times are shown in Tables 1-8 below.

[0048] Table 1 Release data of Example 1 of the present application after different storage times Table 2 Release data of Example 2 of the present application after different storage times Table 3 Release data of Example 3 of the present application after different storage times Table 4 Release data of Example 4 of the present application after different storage times Table 5 Release data of Example 5 of the present application after different storage times Table 6 Release data of Example 6 of the present application after different storage times Table 7 Release data of Example 7 of the present application after different storage times Table 8 Release data of Example 8 of the present application after different storage times The release results of the verapamil hydrochloride sustained-release capsules of Comparative Examples 1-5 at different storage times are shown in Tables 9-13 below.

[0049] Table 9 Release data of Comparative Example 1 of the present application after different storage times Table 10 Release data of Comparative Example 2 of the present application after different storage times Table 11 Release data of the present application comparative example 3 after different storage time Table 12 Release data of the present application comparative example 4 after different storage time Table 13 Release data of the present application comparative example 5 after different storage time Note: The release data in the tables 11-13 "-" means that the similarity factor f2 of the release at the last storage time point and the initial product has been less than 50, so no more sampling detection is needed.

[0050] From the test results of the examples 1-8 in the tables 1-8, it can be seen that when the release stabilizer hydroxypropyl methyl cellulose E5 and / or ethyl cellulose N7 accounts for 12%-26% of the weight of the content of the sustained release capsules, the release similarity factor of the prepared sustained release capsules after 6 months of storage at 40℃, RH 75% can reach more than 50, which confirms that the release stabilizer hydroxypropyl methyl cellulose E5 and / or ethyl cellulose N7 can keep the release of verapamil hydrochloride sustained release capsules unchanged during storage, ensuring the clinical use safety of the drug within the shelf life.

[0051] In comparison, from the test results of the comparative examples 1-2 in the tables 9-10, it can be seen that when the amount of release stabilizer in the prescription is less than 12%, the release similarity factor of the prepared sustained release capsules after 6 months of storage cannot reach 50. From the test results of the comparative examples 3-5 in the tables 11-13, it can be seen that when the release stabilizer (povidone K29 / 32 or hydroxypropyl cellulose EXF) used in the prescription, the release similarity factor of the prepared sustained release capsules after 1-3 months of storage cannot reach 50. The above test results show that only the specific type of release stabilizer of the present application is used and the specific amount is used, the verapamil hydrochloride sustained release capsules can obtain the similar in vitro dissolution rate to the initial product during long-term storage, ensuring the drug quality during storage.

[0052] Although specific embodiments of the present application have been described, those skilled in the art will recognize that various modifications and changes can be made to the present application without departing from the scope or spirit of the present application. Thus, the present application is intended to cover all such modifications and changes that come within the scope of the appended claims and their equivalents.

Claims

1. A method for improving the release stability of verapamil hydrochloride sustained-release capsules during storage, characterized in that, The sustained-release capsule contents comprise sustained-release coated microspheres, the sustained-release coated microspheres comprising: (a) a blank core, (b) a drug coating layer surrounding the blank core, and (c) a sustained-release coating layer surrounding the drug coating layer; the method comprises adding a release stabilizer to the drug coating layer containing verapamil hydrochloride, and after long-term storage at 40°C and 75% RH, the in vitro release similarity factor f2 of the sustained-release capsules before storage is greater than 50.

2. The method according to claim 1, characterized in that, The release stabilizer is selected from one or more of hydroxypropyl methylcellulose and ethylcellulose.

3. The method according to claim 1, characterized in that, The blank pellet core is selected from one or more of sucrose, starch, lactose, and microcrystalline cellulose.

4. The method according to claim 1, characterized in that, The sustained-release coating layer comprises a sustained-release material, a plasticizer, and an anti-sticking agent.

5. The method according to claim 4, characterized in that, The sustained-release material is selected from one or more of ethyl cellulose, acrylic resin, and cellulose acetate.

6. The method according to claim 4, characterized in that, The plasticizer is selected from one or more of triethyl citrate, diethyl phthalate, and dibutyl sebacate.

7. The method according to claim 4, characterized in that, The anti-adhesion agent is selected from one or more of magnesium stearate, glyceryl monostearate, and talc.

8. A verapamil hydrochloride sustained-release capsule with stable release during storage, characterized in that, The sustained-release capsule contents comprise sustained-release coated microspheres, each microsphere comprising: (a) a blank core, (b) a drug coating layer surrounding the blank core, and (c) a sustained-release coating layer surrounding the drug coating layer; the drug coating layer comprises verapamil hydrochloride and a release stabilizer, and the in vitro release similarity factor f2 of the sustained-release capsule after long-term storage at 40°C and RH75% is greater than 50 compared to the sustained-release capsule before storage.

9. A method for preparing verapamil hydrochloride sustained-release capsules according to claim 8, characterized in that, The method includes the following steps: (1) Dissolve the prescribed amount of verapamil hydrochloride and release stabilizer material in a mixed solvent to prepare a drug-coated solution; (2) In a fluidized bed coating machine, the drug-containing coating solution prepared in step (1) is slowly sprayed onto the blank pellet core of the prescription amount so that the blank pellet core is coated with a drug coating layer. After drying, drug-containing micro pellets are prepared. (3) Dissolve the prescribed amount of sustained-release material, plasticizer and anti-adhesive in a solvent to prepare a sustained-release coating solution; (4) In a fluidized bed coating machine, the sustained-release coating solution prepared in step (3) is slowly sprayed onto the drug-containing microspheres prepared in step (2) so that the drug-containing microspheres are coated with a sustained-release coating layer. After drying, sustained-release coated microspheres are obtained. (5) Mix the sustained-release coated microspheres obtained in step (4) with a lubricant and fill them into capsules to obtain the final product.

10. The use of the verapamil hydrochloride sustained-release capsules according to claim 8 in the preparation of a medicament for treating essential hypertension, angina pectoris, or arrhythmia.

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